Thiazolidinetriones



, 3,252,988 Ice Patented May 24, 1966 3,252,988 THIAZOLIDINETRIONES t Paul J. Stofiel, St. Louis, Mo., assignor to Monsanto Company, a corporation of Delaware 0 N S No Drawing. Filed Sept. 23, 1963, Ser. No. 310,883 5 6 18 Claims. (Cl. 260-3063) ()1 H H O O This invention relates to a novel chemical process and E am I 2 to new compounds prepared thereby. The new comx p 8 pounds are biological toxicants useful as herbicides and The preceding procedure was repeated using methyl in the control of objectionable microorganisms. The 10 Nmethylthionocarbamate in place of the isopropyl 3,4 compounds are also useful intermediates in the preparadichlorothionocarbanilate. A product identified as that tion of other biologically active compounds. having the following structure was formed.

The new procedure may be defined structurally by the 0 equation: I!

HsC-N-C-S l? O=OC=O H (I? 1 /C\ Example 3 R"NHC 901 1 S The reaction product of oxalyl chloride and benzyl N- =cc=0 4-ethoxythionocarbanilate was identified as that having the structure: in which R and R are selected from the class consisting of hydrocarbon radicals selected from the class consist- H ing of alkyl radicals of up to 12 carbon atoms, alkenyl a 2 lTI radicals of up to 12 carbon atoms, cycloalkyl having from four to eight carbon atoms, phenyl and benzyl; and

the said hydrocarbon radicals containing up to four substituents selected from the group consisting of chlorine, Example 4 brom1ne, nitro, alkyl having up to four carbon atoms, al- The procedure of Example 1 was repeated using methyl koxy having up to four carbon atoms and phenyl cyclohexylthionocarbamate in place of isopropyl 3,4-di- This reaction is effected by combining the reagents to produce an exothermic reaction. The rearrangement of the thiono sulfur atom to form a thiazolidinetrione may chlorothionocarbanilate. The resulting structure was found to characterize the Product:

be accomplished at moderate temperatures, for example E 30 to 80 C. generated as the heat of reaction. If de- CH: CHNC-S sired to complete the reaction, additional heating may be used, for example from 80 to 180 C. Further heating is undesirable because it will frequently induce decom- Example 5 position of the product. A xylene solution of allyl N-allylthionocarbamate was To control the rate of reaction, the reaction mixture 40 treated with a slight excess of oxalyl chloride. When the may be diluted with a suitable inert solvent, for example reaction temperature subsided an equal volume of hexane the aromatic hydrocarbons and halogen substituted hy was added. The product precipitated Was identified as drocarbons, such as benzene, chlorobenzene, toluene, having the structure:

chlorotoluene, xylene, 1,4-dichlorobenzene, etc. 0

The reaction may be efficiently controlled by dissolvll ing one reagent in the solvent medium and gradually add- GHFC H CHZ 1\|IC"S ing thereto the second reagent. 0=CC=O The reaction between oxalyl chloride and the esters Example 5 of the thionocarbamic acids are continued until substantial completion as evidenced by the subsidence of the reaction temperature. The product may be separated from the solvent medium by adding to the solvent a miscible solvent which is a non-solvent for the product. This will reduce the solubility of the product in the reaction mixture Using the procedure of Example 1 except the flask was charged with a stoichiometric proportion of ethyl 3,4- dichlorothionocarbanilate. The addition of oxalyl chloride formed a product identical to that of Example 1 with the structure:

and induce the precipitation of the product. The crude 0 product may then be purified by recrystallization from a C1 suitable solvent, for example acetone or ether. Further details of the preparations and the products so 01 formed are set forth in the following specific examples. 0 0

Example 7 Example 1 The reaction of equimolar proportions of oxalyl chloride and phenyl N-4-methyloxybenzylthionocarbamate A reaction flask was charged with 50 ml. of toluene produced a Compound of the Structure:

and 26.4 grams of isopropyl-3,4-dichlorothionocarbanilate. The reaction was effected by the gradual addition of 12.7 grams of oxalyl chloride. The reaction was exo- CH;OGH NO-s thermic. Throughout the reaction HCl was evolved :0 and when the reaction subsided the mixture was stirred for one hour. With continued stirring 250 ml. of hexane Example 8 was added and the product precipitated in the form of Using the procedural details of Example 1 oxalyl chlo- White crystals (MJP. 179.9180.5 C.). The compound ride and methyl thionocarbanilate were reacted to form was found to have the structure: a compound of the structure:

Example 9 The procedure of Example 8 was repeated substituting methyl methoxythionocarbanilate for the methyl thionocarbanilate. The following compound was formed:

Examples to 12 Using the procedures of Examples 1 to 9 and selected thiocarbanilates, compounds of the following formulae can be prepared:

Examples 13 to I 6 Useful compounds may also be prepared by reacting the following thionocarbanilate esters with oxalyl chloride by the procedures described in Examples 1 to 9:

Cl S Although the invention is described with respect to specific modifications, it is not intended that the details thereof are limitations on the scope of the invention except to the extent incorporated in the following claims.

What is claimed is:

1. A compound of the formula:

wherein R is selected from the class consisting of hydrocarbon selected from the class consisting of alkyl of up to 12 carbon atoms, alkenyl of up to 12 carbon atoms, cycloalkyl having from 4 to 8 carbon atoms, phenyl and benzyl; and said hydrocarbon containing up to four substituents selected from the group consisting of chlorine,

comprises heating oxalyl chloride with esters of thionocarbamic acid having the formula:

RNC")S o=C-o=o wherein R is an alkyl having up to 12 carbon atoms.

4. The method of preparing thiazolidinetriones which comprises heating at reflux temperatures in an inert solvent medium oxalyl chloride and a thionocarbamic acid ester of the formula:

wherein both R and R are alkyl of up to 12 carbon atoms.

5. A compound of the formula:

wherein n is an integer from one to five.

6. The method of preparing thiazolidinetriones which comprises heating at reflux temperatures in an inert solvent medium oxalyl chloride and an alkyl N-cycloalkyl thionocarbamate, wherein the alkyl has up to 12 carbon atoms and the cycloalkyl radical has from four to eight carbon atoms.

7. A compound of the formula:

wherein n is an integer from one to four.

8. The method of preparing compounds of the formula:

which comprises heating at the reflux temperature in an inert solvent medium oxalyl chloride and an alkyl thionocarbamate of the formula:

wherein R is alkyl of up to 12 carbon atoms and n is an integer from one to four.

9. N-methyl thiazolidinetrione.

10. The method of preparing N-methyl thiazolidinetrione which comprises heating in an aromatic hydrocarbon medium oxalyl chloride and methyl N-methylthiono- I carbamate.

bromine, nitro, alkyl of up to four carbon atoms, alkoxy having up to four carbon atoms and phenyl.

2. The method of preparing thiazolidinetriones which 11. N-cyclohexyl thiazolidinetrione.

12. The method of preparing N-cyclohexyl thiazolidinetrione which comprises heating in an aromatic hydrocarbon medium oxalyl chloride and ethyl N-cyclohexylthionocarbamate.

13. N-3,4-dichlorophenyl thiazolidinetrione.

14. The method of preparing N-3,4-dichlorophenyl 18. The method of preparing N-phenyl thiazolidinethiazolidinetrione which comprises heating in an aromatic trione which comprises heating in an aromatic hydrocarhydrocarbon di l l hl id d th l 3,4. bou medium oxalyl chloride and methylthionocarbanilate.. dichlorothionocarbanilate.

15. N-4-methoxypheny1 thiazolidinetrione. 5 References Cited by the Examiner 15. The method of preparing N-4-methoxypher1yl thi- Burger: Medicinal Chemistry (New York, 1960), pages azolidinetrione which comprises heating in an aromatic 77-81.

hydrocarbon medium oxalyl chloride and methyl 4-ethoxythionocarbanilate NICHOLAS S. RIZZO, Primary Exammer.

17. N-phenyl thiazolidinetrionc. 10 ALTON D. ROLLINS, Assistant Examiner. 

1. A COMPOUND OF THE FORMULA:
 2. THE METHOD OF PREPARING THIAZOLIDINETRIONES WHICH COMPRISES HEATING OXALYL CHLORIDE WITH ESTERS OF THIONOCARBAMIC ACID HAVING THE FORMULA: 